Katherine Leung

Association between carbohydrate intake and serum lipids

Background: The effect of dietary carbohydrate on blood lipids has received considerable attention in light of the current trend in lowering carbohydrate intake for weight loss. Objectives: To evaluate the association between carbohydrate intake and serum lipids. Methods: Blood samples and 24-hour dietary and physical activity recall interviews were obtained from each subject at quarterly intervals for five consecutive quarters between 1994 and 1998 from 574 healthy adults in Central Massachusetts. Relationships between serum lipids and dietary carbohydrate factors were assessed using linear mixed models and adjusting for other risk factors known to be related to blood lipids. Both cross-sectional and longitudinal results were reported. Results: Cross-sectional analysis results from this study suggest that higher total carbohydrate intake, percentage of calories from carbohydrate, glycemic index (GI) and/or glycemic load (GL) are related to lower high-density lipoprotein cholesterol (HDL-C) and higher serum triacylglycerol levels, while higher total carbohydrate intake and/or GL are related to lower total and low-density lipoprotein cholesterol (LDL-C) levels. In a one-year longitudinal analysis, GL was positively associated with total and LDL-C levels, and there was an inverse association between percentage of calories from carbohydrate and HDL-C levels. Conclusions: Results suggest that there is a complex and predominantly unfavorable effect of increased intake of highly processed carbohydrate on lipid profile, which may have implications for metabolic syndrome, diabetes, and coronary heart disease. Further studies in the form of randomized controlled trials are required to investigate these associations and determine the implications for lipid management.

Social Support to Empower Parents (STEP) An Intervention for Parents of Young Children Newly Diagnosed With Type 1 Diabetes

Purpose The purpose of this study was to test the efficacy of a social support intervention with parents of children <13 years old newly diagnosed with type 1 diabetes mellitus (T1DM). Methods For this randomized, controlled clinical trial, 10 parent mentors of children diagnosed with T1DM ≥1 year and 60 parent participants were recruited from 2 pediatric diabetes centers. Mentors were trained to provide social support (home visits and phone calls) for 12 months to families in the experimental arm (32 mothers). Control group parents (28 mothers) received the phone number of an experienced parent (not trained to give social support) to call as needed. Findings Mothers in the experimental and control arms differed at baseline only in birth order of the child with T1DM. The 2 groups did not differ significantly at 3, 6, or 12 months in parent concern, confidence, worry, impact on the family, or perceived social support. Mothers in the experimental arm identified the parent mentor as someone they would seek for advice and issues regarding growth and development, sleep, eating habits, and identification of community agencies. Parent mentors consistently referred mothers to health care providers for advice on medications and treatments but helped them incorporate this advice into day-to-day management. Conclusion Mothers in the experimental arm valued the mentors’ help in adjusting to the diagnosis, but this value was not measured by the study instruments. Focus group research is under way to clarify the concept of parent mentor social support and to develop a social support measurement tool.

Adverse childhood experiences and chronic hypothalamic–pituitary–adrenal activity

Abstract Inconsistencies exist in the current literature regarding hypothalamic–pituitary–adrenal (HPA) regulation following exposure to repeated stressful events. These inconsistencies stem, in part, from the limitations imposed by measuring cortisol in saliva or plasma (i.e. “point measures” of HPA activity). The present study used a cross-sectional, correlational design to examine the relationship between childhood stress (assessed using the adverse childhood experiences [ACEs] questionnaire) and hair cortisol (a biomarker of chronic HPA activity) in 55 healthy 18–24-year-old college students. Dichotomous ACE score for two models using different cut-points was significantly, inversely related to hair cortisol level (B = 1.03, p = 0.046 and B = 1.09, p = 0.031). These results are consistent with theoretical models where exposure to repeated stressful events results in chronic HPA dysregulation, which may include down-regulation under certain conditions.

Dietary phytoestrogen intakes and cognitive function during the menopausal transition: results from the Study of Women's Health Across the Nation Phytoestrogen Study.

ObjectivePhytoestrogens, which consist mainly of isoflavones, lignans, and coumestans have estrogenic and anti-inflammatory properties. Previous research suggests that higher dietary or supplemental intakes of isoflavones and lignans are related to better cognitive performance in middle-aged and older women. MethodsWe conducted longitudinal analysis of dietary phytoestrogens and cognitive performance in a cohort of African American, white, Chinese, and Japanese women undergoing the menopausal transition. The tests were Symbol Digit Modalities, East Boston Memory, and Digits Span Backward. Phytoestrogens were assessed using the Food Frequency Questionnaire. We modeled each cognitive score as a function of concurrent value of the primary predictors (highest tertile of isoflavones, lignans, or coumestrol) and covariates including the menopausal transition stage. ResultsCoumestrol and isoflavone intakes were 10 and 25 times greater, respectively, in Asian than in non-Asian participants. During late perimenopause and postmenopause, Asian women with high isoflavone intakes did better on processing speed, but during early perimenopause and postmenopause, high-isoflavone Asian consumers performed worse on verbal memory. The highest isoflavone consumers among non-Asians likewise posted lower verbal memory scores during early perimenopause. A verbal memory benefit of higher dietary lignan consumption was apparent only during late perimenopause, when women from all ethnic/racial groups who were in the highest tertile of intake demonstrated a small advantage. Coumestrol was unrelated to cognitive performance. ConclusionsThe cognitive effects of dietary phytoestrogens are small, seem to be class-specific, vary by menopause stage and cognitive domain, and differ among ethnic/racial groups (but whether this is related to dose or to host factors cannot be discerned).

Activating peripheral arterial disease patients to reduce cholesterol: a randomized trial

BACKGROUND Peripheral arterial disease patients are less likely than other high-risk patients to achieve ideal low-density lipoprotein (LDL) cholesterol levels. This randomized controlled trial assessed whether a telephone counseling intervention, designed to help peripheral arterial disease patients request more intensive cholesterol-lowering therapy from their physician, achieved lower LDL cholesterol levels than 2 control conditions. METHODS There were 355 peripheral arterial disease participants with baseline LDL cholesterol ≥70 mg/dL enrolled. The primary outcome was change in LDL cholesterol level at 12-month follow-up. There were 3 parallel arms: telephone counseling intervention, attention control condition, and usual care. The intervention consisted of patient-centered counseling, delivered every 6 weeks, encouraging participants to request increases in cholesterol-lowering therapy from their physician. The attention control condition consisted of telephone calls every 6 weeks providing information only. The usual care condition participated in baseline and follow-up testing. RESULTS At 12-month follow-up, participants in the intervention improved their LDL cholesterol level, compared with those in attention control (-18.4 mg/dL vs -6.8 mg/dL, P=.010) but not compared with those in usual care (-18.4 mg/dL vs -11.1 mg/dL, P=.208). Intervention participants were more likely to start a cholesterol-lowering medication or increase their cholesterol-lowering medication dose than those in the attention control (54% vs 18%, P=.001) and usual care (54% vs 31%, P <.001) conditions. CONCLUSION Telephone counseling that helped peripheral arterial disease patients request more intensive cholesterol-lowering therapy from their physician achieved greater LDL cholesterol decreases than an attention control arm that provided health information alone.

Helping men make an informed decision about prostate cancer screening: A pilot study of telephone counseling

OBJECTIVE Evaluate a computer-assisted telephone counseling (CATC) decision aid for men considering a prostate specific antigen (PSA) test. METHODS Eligible men were invited by their primary care providers (PCPs) to participate. Those consenting received an educational booklet followed by CATC. The counselor assessed stage of readiness, reviewed booklet information, corrected knowledge deficits and helped with a values clarification exercise. The materials presented advantages and disadvantages of being screened and did not advocate for testing or for not testing. Outcome measures included changes in stage, decisional conflict, decisional satisfaction, perceived vulnerability and congruence of a PSA testing decision with a pros/cons score. Baseline and final surveys were administered by telephone. RESULTS There was an increase in PSA knowledge (p<0.001), and in decisional satisfaction (p<0.001), a decrease in decisional conflict (p<0.001), and a general consistency of those decisions with the mans values. Among those initially who had not made a decision, 83.1% made a decision by final survey with decisions equally for or against screening. CONCLUSIONS The intervention provides realistic, unbiased and effective decision support for men facing a difficult and confusing decision. PRACTICE IMPLICATIONS Our intervention could potentially replace a discussion of PSA testing with the PCP for most men.

Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids

The gap in mortality between patients with rheumatoid arthritis (RA) and the general population (1.5–3.0 fold risk) is increasing. This disparity is attributable mainly to cardiovascular disease (CVD), as the CVD risk is comparable to patients with diabetes mellitus. The purpose of this study is to determine whether borage seed oil rich in gamma-linolenic acid, fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or the combination of both oils are useful treatments for dyslipidemia in patients with RA. We randomized patients into a double blind, 18 month trial. Mixed effects models were used to compare trends over time in serum lipids. No significant differences were observed between the three groups: All three treatment groups exhibited similar meaningful improvement in the lipid profile at 9 and 18 months. When all groups were combined, these treatments significantly reduced total and LDL-cholesterol and triglycerides, increased HDL-cholesterol, and improved the atherogenic index. All improvements observed at 9 months persisted at 18 months (P < 0.001 verses baseline). Conclusion. Marine and botanical oils may be useful treatment for rheumatoid arthritis patients who are at increased risk for cardiovascular disease compared to the general population.

Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: An 18-Month, Randomized, and Double-Blind Trial

Objective. To determine whether a combination of borage seed oil rich in gamma linolenic acid (GLA) and fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is superior to either oil alone for treatment of rheumatoid arthritis (RA). Methods. Patients were randomized into a double-blind, 18-month trial. Mixed effects models compared trends over time in disease activity measures. Results. No significant differences were observed in changes in disease activity among the three randomized groups. Each group exhibited significant reductions in disease activity (DAS28) at 9 months (fish: −1.56[−2.16, −0.96], borage: −1.33[−1.83, −0.84], combined: −1.18[−1.83, −0.54]) and in CDAI (fish: −16.95[−19.91, −13.98], borage: −11.20[−14.21, −8.19], and combined: −10.31[−13.61, −7.01]). There were no significant differences in change of RA medications among the three groups. Reduced disease activity in study patients was similar to matched patients from an RA registry, and reduction in DMARD use was greater (P < 0.03) in study patients. Conclusion. All 3 treatment groups exhibited similar meaningful clinical responses after 9 months, improvements which persisted for 18 months, and a response similar to matched patients from an RA registry. Study patients were able to reduce DMARD therapy given in combination with TNF antagonists to a greater extent than registry patients. This paper is dedicated to the memory of Dr. John T. Sharp, M.D., a pioneer and innovator in the field of musculoskeletal radiology

Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial.

Objective The relatively modest benefit of vasomotor symptom relief in clinical trials of isoflavones may reflect once-daily dosing and low percentages of participants who are able to metabolize daidzein into equol, a potentially more biologically active isoflavone. This pilot study examined whether symptom reduction was greater with more frequent administration and with higher daily doses. In addition, we explored possible effect modification by equol producer status. Methods We randomized 130 perimenopausal (no menses in the past 3 mo) and postmenopausal (≥12 mo of amenorrhea) women with a mean of five or more moderate/severe hot flashes per day to treatment arms with varying total daily isoflavone doses and dosing frequency, separately for equol producers and nonproducers. Participants recorded the daily frequency and severity of hot flashes. Analyses compared mean daily hot flash intensity scores (sum of hot flashes weighted by severity) by total daily dose and by dosing frequency. Dose- and frequency-related differences were also compared for equol producers and nonproducers. Results Hot flash intensity scores were lowest in women randomized to the highest total daily dose (100-200 mg) and in women randomized to the highest dosing frequency (twice daily to thrice daily), with greater benefits on nighttime scores than on daytime scores. Dose- and frequency-related differences were somewhat larger in equol producers than in nonproducers. Conclusions These results suggest that a twice-daily to thrice-daily dosing frequency may improve the benefit of isoflavones for vasomotor symptom relief, particularly in equol producers and for nighttime symptoms. Larger studies are needed to confirm these findings.

Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus

Aims/hypothesisDuring pregnancy, adipose tissue (AT) must expand to support the growing fetus and the future nutritional needs of the offspring. Limited expandability of AT is associated with insulin resistance, attributed to ectopic lipid deposition. This study aimed to investigate human AT expandability during pregnancy and its role in the pathogenesis of gestational diabetes mellitus (GDM).MethodsThis cross-sectional study of omental (OM) and subcutaneous (SQ) AT collected at Caesarean delivery included 11 pregnant and three non-pregnant women with normal glucose tolerance (NGT), five with GDM, three with type 2 diabetes mellitus. Adipocyte size, capillary density, collagen content and capillary growth were measured. Affymetrix arrays and real-time PCR studies of gene expression were performed.ResultsMean OM adipocyte size was greater in women with GDM than in those with NGT (p = 0.004). Mean OM and SQ capillary density was lower in GDM compared with NGT (p = 0.015). Capillary growth did not differ significantly between groups. The most differentially expressed AT transcript when comparing non-pregnant and pregnant women corresponded to the IGF binding protein (IGFBP)-5, the expression levels of which was found by subsequent quantitative real-time PCR to be lower in women with GDM vs women with NGT (p < 0.0001).Conclusions/interpretationThe relative OM adipocyte hypertrophy and decreased OM and SQ capillary density are consistent with impaired AT expandability in GDM. The induction of adipose tissue IGFBP5 in pregnancy and its decrease in GDM point to the importance of the IGF-1 signalling pathway in AT expansion in pregnancy and GDM susceptibility.